Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China.
Aging (Albany NY). 2020 Aug 28;12(16):16437-16456. doi: 10.18632/aging.103710.
The incidence of thyroid cancer remains high worldwide, and papillary thyroid cancer (PTC) is the most common type. Potassium Calcium-Activated Channel Subfamily N Member 4 () has been reported as an oncogene in various cancers. We examined expression of in public databases and discovered that it is upregulated in PTC. We verified this finding using our own validated cohort and RNA sequencing data. We also found that is a diagnostic and prognostic biomarker that is associated with disease-free survival, immune infiltration, and several other clinicopathological features of PTC. Gene Set Enrichment Analysis indicated that apoptotic and epithelial-mesenchymal transition gene sets are both upregulated in PTC patients with higher levels. In PTC cell lines, silencing inhibited cell proliferation, migration and invasion. Moreover, quantitative real-time PCR and Western blotting indicated that silencing increased expression of apoptotic genes in PTC cells and reduced the expression of genes involved in their epithelial-mesenchymal transition. These results suggest that KCNN4 promotes PTC progression by inducing epithelial-mesenchymal transition and suppressing apoptosis, which suggests may be a useful diagnostic and prognostic biomarker of PTC.
甲状腺癌的发病率在全球仍然很高，其中乳头状甲状腺癌（PTC）是最常见的类型。钾钙激活通道亚家族 N 成员 4（KCNN4）已被报道为多种癌症中的癌基因。我们在公共数据库中检查了 KCNN4 的表达，发现其在 PTC 中上调。我们使用自己验证的队列和 RNA 测序数据验证了这一发现。我们还发现，KCNN4 是一种诊断和预后生物标志物，与无病生存率、免疫浸润和 PTC 的其他几种临床病理特征相关。基因集富集分析表明，在 KCNN4 水平较高的 PTC 患者中，凋亡和上皮-间充质转化基因集均上调。在 PTC 细胞系中，沉默 KCNN4 抑制了细胞增殖、迁移和侵袭。此外，实时定量 PCR 和 Western blot 表明，沉默 KCNN4 增加了 PTC 细胞中凋亡基因的表达，并降低了参与上皮-间充质转化的基因的表达。这些结果表明，KCNN4 通过诱导上皮-间充质转化和抑制细胞凋亡促进 PTC 的进展，提示 KCNN4 可能是 PTC 的一种有用的诊断和预后生物标志物。
